Dissecting the genetic predisposition to albuminuria and endothelial dysfunction in a genetic rat model

Abstract

These data demonstrate the partial genetic independence of albuminuria and endothelial dysfunction in this model. From two known albuminuria quantitative trait loci one locus affects both albuminuria and endothelial dysfunction. Whether this observation is based on a common genetic mechanism related to NO availability warrants further investigation.

Endoplasmic reticulum stress inhibition reduces hypertension through the preservation of resistance blood vessel structure and function

“…Images were captured as described above. DHE is oxidized by superoxide in the cell resulting in production of ethidium bromide, which is trapped in the nucleus and emits red fluorescence [31]. Superoxide positivity was quantified by measuring the average fluorescent intensities.…”

Mild caloric restriction reduces blood pressure and activates endothelial AMPK-PI3K-Akt-eNOS pathway in obese Zucker rats

“…Vascular reactivity was performed in an organ bath setting as previously described [31]. Briefly, aortic rings of 2 mm length were given an optimal resting tension of 1.5 g, which was readjusted every 15 min during a 60 min equilibration period.…”

Genetic mechanisms of vascular and renal damage

“…The isolation of causative molecule(s) and pathway(s) underlying susceptibility to vascular damage is only the first step prior to studies on their relevance to human disease. The function of these gene(s)/pathway(s) is still to be determined, but evidence from the study by Steireif et al [5] is tantalizingly pointing toward oxidative stress as the potential mechanism driving genetic susceptibility to endothelial dysfunction and microalbuminuria.…”

“…hypertension). Rodent models of renal and vascular disease including the one reported in this issue of the Journal by Steireif et al [5] have a potential to provide some mechanistic insights into the molecular background of microalbuminuria and vascular damage by using crossbreeding experiments, refined phenotypes, and availability of relevant tissues.…”

“…The study by Steireif et al [5] investigated different measures of endothelial function in the MWF, SHR and WKY, as well as two consomic strains (MWF-6 SHR and MWF-8 SHR ), in which MWF chromosomes 6 and 8 were replaced by the respective chromosomes from SHR (a strain without susceptibility to microalbuminuria). They found that, together with microalbuminuria, the MWF rats exhibited reduced aortic relaxation to acetylcholine, higher contractile susceptibility to noradrenaline stimulation, and increased superoxide anion levels in both arteries and kidneys when compared with the other strains.…”